TY - JOUR
T1 - NCL disease mechanisms
AU - Palmer, David N.
AU - Barry, Lucy A.
AU - Tyynelä, Jaana
AU - Cooper, Jonathan D.
N1 - Funding Information:
The studies from our laboratories were funded from a variety of sources including the US National Institutes of Health , the Neurological Foundation of New Zealand , the Batten Disease Support and Research Association , the Pub Charities New Zealand , the Batten Disease Family Association , the NCL Stiftung , the Natalie Fund , the Wellcome Trust , the European Union (including DEM-CHILD funding from the European Community's Seventh Framework Programme (FP7/2007 — 2013) under Grant Agreement No. 281234 ) and the Academy of Finland .
PY - 2013/11
Y1 - 2013/11
N2 - Despite the identification of a large number of disease-causing genes in recent years, it is still unclear what disease mechanisms operate in the neuronal ceroid lipofuscinoses (NCLs, Batten disease). As a group they are defined by the specific accumulation of protein, either subunit c of mitochondrial ATP synthase or SAPs A and D in lysosome-derived organelles, and regionally specific neurodegeneration. Evidence from biochemical and cell biology studies indicates related lesions in intracellular vesicle trafficking and lysosomal function. There is also extensive immunohistological evidence of a causative role of disease associated neuroinflammation. However the nature of these lesions is not clear nor is it clear why they lead to the defining pathology. Several different theories have proposed a range of potential mechanisms, but it remains to be determined which are central to pathogenesis, and whether there is a mechanism consistent across the group, or if it differs between disease forms. This review summarises the evidence that is currently available and the progress that has been made in understanding these profoundly disabling disorders. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.
AB - Despite the identification of a large number of disease-causing genes in recent years, it is still unclear what disease mechanisms operate in the neuronal ceroid lipofuscinoses (NCLs, Batten disease). As a group they are defined by the specific accumulation of protein, either subunit c of mitochondrial ATP synthase or SAPs A and D in lysosome-derived organelles, and regionally specific neurodegeneration. Evidence from biochemical and cell biology studies indicates related lesions in intracellular vesicle trafficking and lysosomal function. There is also extensive immunohistological evidence of a causative role of disease associated neuroinflammation. However the nature of these lesions is not clear nor is it clear why they lead to the defining pathology. Several different theories have proposed a range of potential mechanisms, but it remains to be determined which are central to pathogenesis, and whether there is a mechanism consistent across the group, or if it differs between disease forms. This review summarises the evidence that is currently available and the progress that has been made in understanding these profoundly disabling disorders. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.
KW - Biochemical abnormalities
KW - Glial activation
KW - Pathogenesis
KW - Selective neuron loss
KW - Storage material accumulation
KW - Synaptic pathology
UR - http://www.scopus.com/inward/record.url?scp=84881552764&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2013.05.014
DO - 10.1016/j.bbadis.2013.05.014
M3 - Review article
C2 - 23707513
AN - SCOPUS:84881552764
SN - 0925-4439
VL - 1832
SP - 1882
EP - 1893
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 11
ER -